An unusual presentation of unifocal Rosai-Dorfman disease and surgical treatment.

Rosai-Dorfman disease (RDD) is a rare histiocytic disorder with an unclear aetiology, and commonly presents with painless, bilateral cervical lymphadenopathy. Extranodal presentation in the absence of nodal involvement has been reported to have a predilection for the head and neck with less than 20 cases involving the jaw bones and sinuses. We present an interesting case of unifocal RDD of the infratemporal space in the absence of nodal involvement in a 61-year-old female treated with surgical excision and adjuvant radiation therapy.

Is the Use of Dexmedetomidine Upon Emergence From Anesthesia Associated With Neck Hematoma Formation Following Head and Neck Microvascular Reconstruction?

BACKGROUND: Dexmedetomidine (DEX) is a highly selective alpha-2-receptor agonist, and its use has not been well studied in major microvascular reconstructive surgery of the head and neck. PURPOSE: The purpose is to measure the association between DEX and neck hematoma formation in subjects undergoing head and neck microvascular reconstructive surgery. STUDY DESIGN, SETTING, SAMPLE: The investigators implemented a retrospective cohort study on subjects undergoing microvascular head and neck reconstruction for benign and malignant pathology at the University of Alabama at Birmingham from 2014 to 2021. Patients with unresectable tumors were excluded. PREDICTOR VARIABLE: The predictor variable was the intraoperative use of DEX upon emergence from general anesthesia. Subjects received standard anesthetic drugs and DEX, while control subjects received only standard anesthetic drugs. MAIN OUTCOME VARIABLE(S): The primary outcome was postoperative neck hematoma formation necessitating a return to the operating theater. The secondary outcome was the length of stay (LOS). COVARIATES: The covariates were demographic, operative, and oral morphine equivalents of anesthesia drugs. ANALYSES: Bivariate analyses were performed using the Student's t-test and the χ2 test for continuous and categorical variables. Multivariate regression analyses were conducted to assess for associations between DEX and the outcomes adjusted for confounding variables when present. P values of < .05 were regarded as statistically significant. RESULTS: A total of 297 subjects (mean age, 59.6 years, and standard deviation [SD], 14.9) with 61.6% male received DEX, and 304 subjects (mean age, 58.9 years, and SD, 14.6) with 60.2% male served as controls (P > .5). A total of 11 postoperative neck hematoma occurred in the control group when compared to 2 in the DEX (relative risk = 5.4, 95% confidence interval [CI], 1.2 to 24, P = .02). The mean LOS was 7.7 (SD, 4.3) and 9.4 (SD, 8.1) for the DEX and control groups (95% CI, 0.7 to 2.8, P < .01). After adjusting for tobacco history, tracheostomy, and neck dissection, DEX (Beta coefficient (B) = -1.7, 95% CI -2.7 to -0.7, P < .01) and neck dissection (B = 2.2, 95% CI 1.0 to 3.4, P < .01) were statistically associated with LOS. CONCLUSION AND RELEVANCE: The use of intraoperative DEX upon emergence from general anesthesia was associated with lower postoperative neck hematoma formation and a shorter length of stay following microvascular head and neck reconstruction.

NLRP6 negatively regulates host defense against polymicrobial sepsis.

Introduction: Sepsis remains a major cause of death in Intensive Care Units. Sepsis is a life-threatening multi-organ dysfunction caused by a dysregulated systemic inflammatory response. Pattern recognition receptors, such as TLRs and NLRs contribute to innate immune responses. Upon activation, some NLRs form multimeric protein complexes in the cytoplasm termed "inflammasomes" which induce gasdermin d-mediated pyroptotic cell death and the release of mature forms of IL-1ß and IL-18. The NLRP6 inflammasome is documented to be both a positive and a negative regulator of host defense in distinct infectious diseases. However, the role of NLRP6 in polymicrobial sepsis remains elusive. Methods: We have used NLRP6 KO mice and human septic spleen samples to examine the role of NLRP6 in host defense in sepsis. Results: NLRP6 KO mice display enhanced survival, reduced bacterial burden in the organs, and reduced cytokine/chemokine production. Co-housed WT and KO mice following sepsis show decreased bacterial burden in the KO mice as observed in singly housed groups. NLRP6 is upregulated in CD3, CD4, and CD8 cells of septic patients and septic mice. The KO mice showed a higher number of CD3, CD4, and CD8 positive T cell subsets and reduced T cell death in the spleen following sepsis. Furthermore, administration of recombinant IL-18, but not IL-1ß, elicited excessive inflammation and reversed the survival advantages observed in NLRP6 KO mice. Conclusion: These results unveil NLRP6 as a negative regulator of host defense during sepsis and offer novel insights for the development of new treatment strategies for sepsis.

Effectiveness of dexmedetomidine during surgery under general anaesthesia on patient-centred outcomes: a systematic review and Bayesian meta-analysis protocol.

INTRODUCTION: Dexmedetomidine is a promising pharmaceutical strategy to minimise opioid use during surgery. Despite its growing use, it is uncertain whether dexmedetomidine can improve patient-centred outcomes such as quality of recovery and pain. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis following the recommendations of the Cochrane Handbook for Systematic Reviews. We will search MEDLINE, Embase, CENTRAL, Web of Science and CINAHL approximately in October 2023. We will include randomised controlled trials evaluating the impact of systemic intraoperative dexmedetomidine on patient-centred outcomes. Patient-centred outcome definition will be based on the consensus definition established by the Standardised Endpoints in Perioperative Medicine initiative (StEP-COMPAC). Our primary outcome will be the quality of recovery after surgery. Our secondary outcomes will be patient well-being, function, health-related quality of life, life impact, multidimensional assessment of postoperative acute pain, chronic pain, persistent postoperative opioid use, opioid-related adverse events, hospital length of stay and adverse events. Two reviewers will independently screen and identify trials and extract data. We will evaluate the risk of bias of trials using the Cochrane Risk of Bias Tool (RoB 2.0). We will synthesise data using a random effects Bayesian model framework, estimating the probability of achieving a benefit and its clinical significance. We will assess statistical heterogeneity with the tau-squared and explore sources of heterogeneity with meta-regression. We have involved patient partners, clinicians, methodologists, and key partner organisations in the development of this protocol, and we plan to continue this collaboration throughout all phases of this systematic review. ETHICS AND DISSEMINATION: Our systematic review does not require research ethics approval. It will help inform current clinical practice guidelines and guide development of future randomised controlled trials. The results will be disseminated in open-access peer-reviewed journals, presented at conferences and shared among collaborators and networks. PROSPERO REGISTRATION NUMBER: CRD42023439896.

Intraoperative pharmacologic opioid minimisation strategies and patient-centred outcomes after surgery: a scoping review.

BACKGROUND: Postoperative patient-centred outcome measures are essential to capture the patient's experience after surgery. Although a large number of pharmacologic opioid minimisation strategies (i.e. opioid alternatives) are used for patients undergoing surgery, it remains unclear which strategies are most promising in terms of patient-centred outcome improvements. This scoping review had two main objectives: (1) to map and describe evidence from clinical trials assessing the patient-centred effectiveness of pharmacologic intraoperative opioid minimisation strategies in adult surgical patients, and (2) to identify promising pharmacologic opioid minimisation strategies. METHODS: We searched MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases from inception to February 2023. We included trials investigating the use of opioid minimisation strategies in adult surgical patients and reporting at least one patient-centred outcome. Study screening and data extraction were conducted independently by at least two reviewers. RESULTS: Of 24,842 citations screened for eligibility, 2803 trials assessed the effectiveness of intraoperative opioid minimisation strategies. Of these, 457 trials (67,060 participants) met eligibility criteria, reporting at least one patient-centred outcome. In the 107 trials that included a patient-centred primary outcome, patient wellbeing was the most frequently used domain (55 trials). Based on aggregate findings, dexmedetomidine, systemic lidocaine, and COX-2 inhibitors were promising strategies, while paracetamol, ketamine, and gabapentinoids were less promising. Almost half of the trials (253 trials) did not report a protocol or registration number. CONCLUSIONS: Researchers should prioritise and include patient-centred outcomes in the assessment of opioid minimisation strategy effectiveness. We identified three potentially promising pharmacologic intraoperative opioid minimisation strategies that should be further assessed through systematic reviews and multicentre trials. Findings from our scoping review may be influenced by selective outcome reporting bias. STUDY REGISTRATION: OSF - https://osf.io/7kea3.

Role of toll-like receptors and nod-like receptors in acute lung infection.

The respiratory system exposed to microorganisms continuously, and the pathogenicity of these microbes not only contingent on their virulence factors, but also the host's immunity. A multifaceted innate immune mechanism exists in the respiratory tract to cope with microbial infections and to decrease tissue damage. The key cell types of the innate immune response are macrophages, neutrophils, dendritic cells, epithelial cells, and endothelial cells. Both the myeloid and structural cells of the respiratory system sense invading microorganisms through binding or activation of pathogen-associated molecular patterns (PAMPs) to pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) and NOD-like receptors (NLRs). The recognition of microbes and subsequent activation of PRRs triggers a signaling cascade that leads to the activation of transcription factors, induction of cytokines/5chemokines, upregulation of cell adhesion molecules, recruitment of immune cells, and subsequent microbe clearance. Since numerous microbes resist antimicrobial agents and escape innate immune defenses, in the future, a comprehensive strategy consisting of newer vaccines and novel antimicrobials will be required to control microbial infections. This review summarizes key findings in the area of innate immune defense in response to acute microbial infections in the lung. Understanding the innate immune mechanisms is critical to design host-targeted immunotherapies to mitigate excessive inflammation while controlling microbial burden in tissues following lung infection.

Evolving Advance Care Planning in a Health Ecosystem: The Kaiser Permanente Experience.

BACKGROUND: Advance care planning is an integral part of supporting patients through serious illness and end-of-life care. PROBLEM: Several components of advance care planning may be too inflexible to account for patients' changing disease and evolving goals as serious illness progresses. Health systems are starting to implement processes to address these barriers, though implementation has varied. PROPOSED SOLUTION: In 2017, Kaiser Permanente introduced Life Care Planning (LCP), incorporating advance care planning dynamically into concurrent disease management. LCP provides a framework for identifying surrogates, documenting goals, and eliciting patient values across disease progression. LCP provides standardized training to facilitate communication and utilizes a centralized section within the electronic health record for longitudinal documentation of goals. OUTCOMES: More than 6000 physicians, nurses, and social workers have been trained in LCP. Over one million patients have engaged in LCP since its inception, with over 52% of patients age 55+ having a surrogate designated. There is evidence of high treatment concordance with patients' desired wishes (88.9%), with high rates of advance directive completion as well (84.1%).

Supplemental Regional Block Anesthesia Reduces Opioid Utilization Following Free Flap Reconstruction of the Oral Cavity: A Prospective, Randomized Clinical Trial.

PURPOSE: Regional anesthesia has been shown to effectively manage acute pain and reduce opioid utilization in the early postoperative period following colorectal, orthopedic, and thoracic surgeries. The same effect, however, has not been demonstrated in major head and neck surgery. The purpose of this study is to determine whether supplemental regional anesthesia reduces opioid utilization following microvascular free flap reconstruction of the oral cavity. METHODS: A prospective, randomized clinical trial was conducted for patients undergoing oral cavity reconstruction using microvascular free tissue transfer between January 2020 and March 2022. The predictor variable was a regional anesthetic nerve block, delivered preoperatively, at the flap donor site. The primary and secondary outcomes were opioid utilization, measured in oral morphine equivalent (OME), from postoperative day 1 to 5, and hospital length of stay (LOS), respectively. Covariates included age, sex, tobacco and alcohol history, prior radiation therapy, pathology, oral site, flap type, tracheostomy, and neck dissection. Student's t test, χ2 test, and linear regression models were computed using correlations with 95% confidence intervals (CIs). For all statistical tests, P values of <.05 were regarded as statistically significant. RESULTS: Ninety-eight participants completed the study. The mean age was 56 years with 55% male. Forty-eight patients received a presurgical regional anesthesia block, and 50 patients served as control subjects. Bivariate analysis demonstrated an even distribution of all study variables. Total OME utilization was significantly less in the treatment group compared to the control group, (166.32 vs 118.43 OME; 95% CI, 1.32 to 94.45; P = .04). The LOS was comparable (6.60 vs 6.48 days; 95% CI, -0.53 to 0.77; P = .71). Tobacco use had a positive effect (B = 0.28; 95% CI, 21.63 to 115.31; P = .005) while the block had a negative effect with total OME, (B = -0.19; 95% CI, -90.39 to -0.59; P = .047). The extent of the neck dissection (B = 0.207; 95% CI, 0.026 to 1.403; P = .042) was a positive predictor for LOS. Overall, there were no adverse events associated with the regional block throughout the study period. CONCLUSIONS: Supplemental regional anesthesia is safe and associated with reduced opioid utilization in patients undergoing vascularized free flap reconstruction of composite oral cavity defects and does not prolong the length of hospitalization.

Racial Disparities and Mental Health Effects Within Prostate Cancer.

Disparities in prostate cancer (PCa) exist at all stages: screening, diagnosis, treatment, outcomes, and mortality. Although there are a multitude of complex biological (e.g., genetics, age at diagnosis, PSA levels, Gleason score) and nonbiological (e.g., socioeconomic status, education level, health literacy) factors that contribute to PCa disparities, nonbiological factors may play a more significant role. One understudied aspect influencing PCa patients is mental health related to the quality of life. Overall, PCa patients report poorer mental health than non-PCa patients and have a higher incidence of depression and anxiety. Racial disparities in mental health, specifically in PCa patients, and how poor mental health impacts overall PCa outcomes require further study.

Neurobehavioral deficits and a progressive ictogenesis in the tetrodotoxin model of epileptic spasms.

OBJECTIVE: Our goal was to determine whether animals with a history of epileptic spasms have learning and memory deficits. We also used continuous (24/7) long-term electroencephalographic (EEG) recordings to evaluate the evolution of epileptiform activity in the same animals over time. METHODS: Object recognition memory and object location memory tests were undertaken, as well as a matching to place water maze test that evaluated working memory. A retrospective analysis was undertaken of long-term video/EEG recordings from rats with epileptic spasms. The frequency and duration of the ictal events of spasms were quantified. RESULTS: Rats with a history of epileptic spasms showed impairment on the three behavioral tests, and their scores on the object recognition memory and matching to place water maze tests indicated neocortical involvement in the observed impaired cognition. Analysis of EEG recordings unexpectedly showed that the ictal events of spasms and their accompanying behaviors progressively increased in duration over a 2-week period soon after onset, after which spasm duration plateaued. At the same time, spasm frequency remained unchanged. Soon after spasm onset, ictal events were variable in wave form but became more stereotyped as the syndrome evolved. SIGNIFICANCE: Our EEG findings are the first to demonstrate progressive ictogenesis for epileptic spasms. Furthermore, in demonstrating cognitive deficits in the tetrodotoxin model, we have met a criterion for an animal model of West syndrome. Animal models will allow in-depth studies of spasm progression's potential role in cognitive regression and may elucidate why early treatment is considered essential for improved neurodevelopmental outcomes in children.

Does Early Oral Intake After Microvascular Free Flap Reconstruction of the Oral Cavity Lead to Increased Postoperative Complications?

PURPOSE: Data on timing of oral intake (PO) after free flap reconstruction of the oral cavity have been limited. Recent studies have shown that early PO after free flap reconstruction does not lead to increased morbidity and has resulted in decreased hospital stay. The objective of this study is to assess postoperative complications associated with timing of PO after free flap reconstruction of the oral cavity and to define clinical predictors of postoperative complications. METHODS: This was a retrospective comparative cohort study and comprised of patients who underwent free flap reconstruction of the oral cavity between January 2014 and December 2019 in the Department of Oral and Maxillofacial Surgery at the University of Alabama at Birmingham. The predictor variable was timing of PO grouped into early (<5 days) and late (>5 days), postoperatively. The primary and secondary outcomes were postoperative complications and hospital length of stay (LOS), respectively. Covariates included age, gender, pathology, reconstruction site, flap type, tracheostomy, neck dissection, defect volume (cm3), skin paddle size (cm2), and gastrostomy tube (g-tube). Student's t-test, Chi-squared test, and binary logistic regression models were computed using odds ratios (ORs) with 95% confidence intervals (CIs). For all statistical tests, P values of < .05 were regarded as statistically significant. RESULTS: The sample consisted of 415 patients (253 males and 162 females), with a mean age of 58.8 years (range, 14.4-88.2 years). The majority had malignant pathology (68.9%) with defects involving the mandible (52.3%) and reconstructed with a radial forearm (43.6%), followed by fibula (39%), and osteocutaneous radial forearm (13%). Seventy one "early PO" and 344 "late PO" patients were analyzed. Early PO was associated with lower postoperative complications compared with the late PO group (RR = 0.847, 95% CI 0.747-0.960, P = .031) and shorter hospital LOS (6 vs 9 days, 95% CI 2.2459-3.720, P < .001). A regression model showed a 2% increase for postoperative complications with each unit (cm3) increase of defect volume (OR = 1.002, 95% CI 1.000-1.004, P = .035) and 2.286 times higher odds for postoperative complication in patients with a g-tube (95% CI 1.271-4.110, P = .006). CONCLUSIONS: Early PO after free flap reconstruction of the oral cavity was not associated with increased postoperative outcomes or delayed hospital course. Variables such as defect location, defect volume, and tracheostomy may increase the risk for postoperative complications and can help guide surgeons in deciding the optimal timing for PO postoperatively.

Pharmacologic Manipulation of Late SV40 Factor Suppresses Wnt Signaling and Inhibits Growth of Allogeneic and Syngeneic Colon Cancer Xenografts.

Aberrant hyperactivation of Wnt signaling, driven by nuclear ß-catenin in the colonic epithelium, represents the seminal event in the initiation and progression of colorectal cancer (CRC). Despite its established role in CRC tumorigenesis, clinical translation of Wnt inhibitors remains unsuccessful. Late SV40 factor (LSF; encoded by TFCP2) is a transcription factor and a potent oncogene. The current study identified a chemotype, named factor quinolinone inhibitors (FQIs), that specifically inhibits LSF DNA-binding, partner protein-binding, and transactivation activities. The role of LSF and FQIs in CRC tumor growth was examined. Herein, the study showed that LSF and ß-catenin interacted in several CRC cell lines irrespective of their mutational profile, which was disrupted by FQI2-34. FQI2-34 suppressed Wnt activity in CRC cells in a dose-dependent manner. Leveraging both allogeneic and syngeneic xenograft models showed that FQI2-34 suppressed CRC tumor growth, significantly reduced nuclear ß-catenin, and down-regulated Wnt targets such as axis inhibition protein 2 (AXIN-2) and SRY-box transcription factor 9, in the xenograft cells. FQI2-34 suppressed the proliferation of xenograft cells. Adenocarcinomas from a series of stage IV CRC patients revealed a positive correlation between LSF expression and Wnt targets (AXIN-2 and SRY-box transcription factor 9) within the CRC cells. Collectively, this study uncovers the Wnt inhibitory and CRC growth-suppressive effects of these LSF inhibitors in CRC cells, revealing a novel target in CRC therapeutics.

A Role for Insulin-like Growth Factor 1 in the Generation of Epileptic Spasms in a murine model.

OBJECTIVE: Infantile spasms are associated with a wide variety of clinical conditions, including perinatal brain injuries. We have created a model in which prolonged infusion of tetrodotoxin (TTX) into the neocortex, beginning in infancy, produces a localized lesion and reproduces the behavioral spasms, electroencephalogram (EEG) abnormalities, and drug responsiveness seen clinically. Here, we undertook experiments to explore the possibility that the growth factor IGF-1 plays a role in generating epileptic spasms. METHODS: We combined long-term video EEG recordings with quantitative immunohistochemical and biochemical analyses to unravel IGF-1's role in spasm generation. Immunohistochemistry was undertaken in surgically resected tissue from infantile spasms patients. We used viral injections in neonatal conditional IGF-1R knock-out mice to show that an IGF-1-derived tripeptide (1-3)IGF-1, acts through the IGF-1 receptor to abolish spasms. RESULTS: Immunohistochemical methods revealed widespread loss of IGF-1 from cortical neurons, but an increase in IGF-1 in the reactive astrocytes in the TTX-induced lesion. Very similar changes were observed in the neocortex from patients with spasms. In animals, we observed reduced signaling through the IGF-1 growth pathways in areas remote from the lesion. To show the reduction in IGF-1 expression plays a role in spasm generation, epileptic rats were treated with (1-3)IGF-1. We provide 3 lines of evidence that (1-3)IGF-1 activates the IGF-1 signaling pathway by acting through the receptor for IGF-1. Treatment with (1-3)IGF-1 abolished spasms and hypsarrhythmia-like activity in the majority of animals. INTERPRETATION: Results implicate IGF-1 in the pathogenesis of infantile spasms and IGF-1 analogues as potential novel therapies for this neurodevelopmental disorder. ANN NEUROL 2022;92:45-60.

Computer-Assisted Microvascular Free Flap Reconstruction and Implant Rehabilitation of the Maxilla-Treatment of a Rare Post-orthognathic Complication.

Orthognathic surgery is generally a safe and predictable procedure. Major postoperative complications are rare and often non-life threatening. An example of a rare complication associated with the LeFort I osteotomy is avascular necrosis of the maxilla (ANM). While cases of ANM have been described in the literature, the majority involves only a portion or segment of the maxillary complex and is commonly treated with conservative measures such as strict oral hygiene, hyperbaric oxygen therapy and local debridement. Occasionally, larger segments of osteonecrosis may require extensive reconstruction such as bone grafting with local soft tissue flaps. Here, we present a patient that underwent a single-stage microvascular free tissue reconstruction with concomitant placement of dental implants and a patient-specific implant (PSI) for post-orthognathic ANM.

Combined Nasal Endoscopic and Subfrontal Craniotomy for Resection Tumors of Anterior Skull Base.

OBJECTIVE: Sinonasal tumors invading anterior skull base is difficult to treat in Otorhinolaryngology and Neurosurgery. Treatment requires the collaboration of ear, nose and throat (ENT) and neurosurgeon to remove the tumor completely. This study was to evaluate the outcome of combined technique nasal endoscopic and subfrontal approach in case of sinonasal tumors involving anterior skull base. METHODS: Retrospective cross-sectional study. RESULTS: The study was a cross-sectional study that had taken place at Otorhinolaryngology and Neurosurgery Department of Cho Ray Hospital, Vietnam. All 45 patients were enrolled and underwent the surgery. 71.1% of these cases were malignant tumors. The ratio of sinonasal malignant tumor is squamous cell carcinoma and esthesioneuroblastoma were 24.4% and 11.1%, respectively. All the cases were diagnosed as sinonasal tumor invading anterior skull base and successfully removed by combining nasal endoscopic approach with subfrontal craniotomy. CONCLUSIONS: The combined nasal endoscopic with subfrontal craniotomy for resection nasoethmoid tumor invading the brain show a good result. This technique is an important adjunct that contribute to the treatment of anterior skull base tumor involving the brain.

Complications in oncologic mandible reconstruction: A comparative study between the osteocutaneous radial forearm and fibula free flap.

BACKGROUND: The osteocutaneous radial forearm free flap (OC-RFFF) has been proposed as a safe and reliable free flap for head and neck reconstruction with low donor site morbidity. The purpose of this study is to compare the late complications (>30 days) associated with using the OC-RFFF versus the free fibula flap (FFF) for mandibular reconstruction following oncologic segmental resection. METHODS: We conducted a single-institution, retrospective study composed of patients who underwent oncologic microvascular composite mandibular reconstruction with either the OC-RFFF or FFF. The primary predictor variable was the type of free flap used. The outcome variable was late complication postoperatively (>30 days). RESULTS: A total of 93 patients (28, OC-RFFF and 65, FFF) were analyzed. The majority of patients were male (62%) and with AJCC stage T4a disease (72%). Mean hospital length of stay was comparable between the two flap groups (p = .50). OC-RFFF was associated with more late complications (p = .03) compared to FFF. Nonunion occurred in 10.7% of OC-RFFF and 0% of FFF. Partial or complete flap failure was seen in 7.1% and 0% in the OC-RFFF and FFF, respectively. Two-year disease-free survival was comparable in both groups (p > .05). CONCLUSIONS: The results of this study suggest that the rate of nonunion and odds of having a late complication were significantly greater in the OC-RFFF compared to the FFF following oncologic mandibular reconstruction. However, flap success, early complications (<30 days), and length of hospital stay were comparable between the two flaps.

UTX condensation underlies its tumour-suppressive activity.

UTX (also known as KDM6A) encodes a histone H3K27 demethylase and is an important tumour suppressor that is frequently mutated in human cancers1. However, as the demethylase activity of UTX is often dispensable for mediating tumour suppression and developmental regulation2-8, the underlying molecular activity of UTX remains unknown. Here we show that phase separation of UTX underlies its chromatin-regulatory activity in tumour suppression. A core intrinsically disordered region (cIDR) of UTX forms phase-separated liquid condensates, and cIDR loss caused by the most frequent cancer mutation of UTX is mainly responsible for abolishing tumour suppression. Deletion, mutagenesis and replacement assays of the intrinsically disordered region demonstrate a critical role of UTX condensation in tumour suppression and embryonic stem cell differentiation. As shown by reconstitution in vitro and engineered systems in cells, UTX recruits the histone methyltransferase MLL4 (also known as KMT2D) to the same condensates and enriches the H3K4 methylation activity of MLL4. Moreover, UTX regulates genome-wide histone modifications and high-order chromatin interactions in a condensation-dependent manner. We also found that UTY, the Y chromosome homologue of UTX with weaker tumour-suppressive activity, forms condensates with reduced molecular dynamics. These studies demonstrate a crucial biological function of liquid condensates with proper material states in enabling the tumour-suppressive activity of a chromatin regulator.